tbuckley/cabot-search huggingface dataset:
Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19–Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults — VISION Network, Nine States, September–November 2022
Authors: Mark W. Tenforde, Zachary A. Weber, Karthik Natarajan, Nicola P. Klein, Anupam B. Kharbanda, Edward Stenehjem, Peter J. Embi, Sarah E. Reese, Allison L. Naleway, Shaun J. Grannis, Malini B. DeSilva, Toan C. Ong, Manjusha Gaglani, Jungmi Han, Monica Dickerson, Bruce Fireman, Kristin Dascomb, Stephanie A. Irving, Gabriela Vazquez-Benitez, Suchitra Rao, Deepika Konatham, Palak Patel, Kristin E. Schrader, Ned Lewis, Nancy Grisel, Charlene McEvoy, Kempapura Murthy, Eric P. Griggs, Elizabeth A. K. Rowley, Ousseny Zerbo, Julie Arndorfer, Margaret M. Dunne, Kristin Goddard, Caitlin Ray, Yan Zhuang, Julius Timbol, Morgan Najdowski, Duck-Hye Yang, John Hansen, Sarah W. Ball, Ruth Link-Gelles
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

During June-October 2022, the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the United States, with further Omicron sublineage diversification through November 2022.* Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5 sublineages. On September 1, 2022, a single bivalent booster dose was recommended for adults who had completed a primary vaccination series (with or without subsequent booster doses), with the last dose administered ≥2 months earlier (1). During September 13-November 18, the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose (after 2, 3, or 4 monovalent doses) compared with 1) no previous vaccination and 2) previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses, among immunocompetent adults aged ≥18 years with an emergency department/urgent care (ED/UC) encounter or hospitalization for a COVID-19-like illness.
Neutralization sensitivity, fusogenicity, and infectivity of Omicron subvariants
Authors: Xue-Jun Wang, Lin Yao, Hong-Yun Zhang, Ka-Li Zhu, Jing Zhao, Bing-Dong Zhan, Yi-Ke Li, Xue-Juan He, Cong Huang, Zhuang-Ye Wang, Ming-Dong Jiang, Peng Yang, Yang Yang, Guo-Lin Wang, Sheng-Qi Wang, Er-Hei Dai, Hui-Xia Gao, Mai-Juan Ma
Journal: Genome Medicine (2022)

Abstract Background The emergence of SARS-CoV-2 Omicron subvariants has raised questions regarding resistance to immunity by natural infection or immunization. We examined the sensitivity of Delta and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) to neutralizing antibodies from BBIBP-CorV-vaccinated and BBIBP-CorV- or ZF2001-boosted individuals, as well as individuals with Delta and BA.1 breakthrough infections, and determined their fusogenicity and infectivity. Methods In this cross-sectional study, serum samples from two doses of BBIBP-CorV-vaccinated individuals 1 ( n = 36), 3 ( n = 36), and 7 ( n = 37) months after the second dose; BBIBP-CorV- ( n = 25) or ZF2001-boosted ( n = 30) individuals; and fully vaccinated individuals with Delta ( n = 30) or BA.1 ( n = 26) infection were collected. The serum-neutralizing reactivity and potency of bebtelovimab were assessed against D614G, Delta, and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) through a pseudovirus neutralization assay. The fusogenicity and infectivity of D614G, Delta, and Omicron subvariants were determined by cell-cell fusion assay and pseudovirus infection assay, respectively. Results Omicron subvariants markedly escaped vaccine-elicited neutralizing antibodies after two doses of BBIBP-CorV with comparable efficiency. A third dose vaccination of BBIBP-CorV or ZF2001 increased neutralizing antibody titers and breadth against Delta and three Omicron subvariants. Delta and BA.1 breakthrough infections induced comparable neutralizing antibody titers against D614G and Delta variants, whereas BA.1 breakthrough infections elicited a stronger and broader antibody response against three Omicron subvariants than Delta breakthrough infections. BA.2.12.1 and BA.4/5 are more resistant to immunity induced by breakthrough infections. Bebtelovimab had no significant loss of potency against the Delta and Omicron subvariants. Cell culture experiments showed Omicron subvariants to be less fusogenic and have higher infectivity than D614G and Delta with comparable efficiency. Conclusions These findings have important public health implications and highlight the importance of repeated exposure to SARS-CoV-2 antigens to broaden the neutralizing antibody response against Omicron subvariants.
Adverse Events of Immune Checkpoint Inhibitor-Based Therapies for Unresectable Hepatocellular Carcinoma in Prospective Clinical Trials: A Systematic Review and Meta-Analysis
Authors: Yizhou Zhang, Minghao Wang, Qichen Chen, Yiqiao Deng, Jinghua Chen, Yimin Dai, Sheng Luo, Jianming Xu, Hong Zhao, Jianqiang Cai
Journal: Liver Cancer (2022)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The aim of the study was to investigate the incidence and spectrum of adverse events in unresectable hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs) or ICI-based combinations. &lt;b&gt;&lt;i&gt;Summary:&lt;/i&gt;&lt;/b&gt; The study protocol was prospectively registered on PROSPERO (CRD42022319255). We searched PubMed, EMBASE, and the Cochrane Library for published clinical trials from database inception to April 22, 2022. Studies that included at least one group of unresectable HCC patients treated with ICIs or ICI-based combinations and reported the incidence or spectrum of treatment-related adverse events (trAEs) or immune-related adverse events (irAEs) were eligible. The incidence and spectra of all-grade and grade ≥3 trAEs were the primary outcomes. The profiles of irAEs, the incidence of trAEs leading to treatment discontinuation, and treatment-related mortalities were additional outcomes. We applied random-effects models to pool the incidence and spectra of adverse events. Subgroup analyses and meta-regression were performed. The literature search identified 2,464 records. Twenty studies (4,146 participants with HCC) met the eligibility criteria. The pooled incidences of all-grade trAEs, grade ≥3 trAEs, all-grade irAEs, and grade ≥3 irAEs were 80.1% (95% CI: 73.8–85.2), 35.4% (95% CI: 27.2–44.6), 31.1% (95% CI: 21.0–43.5), and 6.6% (95% CI: 3.6–11.8), respectively. ICIs plus oral targeted agents (all-grade OR = 17.07, 95% CI: 6.05–48.16, &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001; grade ≥3 OR = 9.35, 95% CI: 4.53–19.29, &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001) and ICIs plus intravenous targeted agents (all-grade OR = 4.91, 95% CI: 1.80–13.42, &lt;i&gt;p&lt;/i&gt; = 0.003; grade ≥3 OR = 4.21, 95% CI: 1.42–12.48, &lt;i&gt;p&lt;/i&gt; = 0.012) were associated with increased trAEs compared with monotherapy. The all-grade trAEs with the highest pooled incidences were reactive capillary endothelial proliferation (49.2%, 95% CI: 26.3–72.3), neutropenia (34.6%, 95% CI: 17.1–57.5), and proteinuria (32.8%, 95% CI: 19.8–49.2). The grade ≥3 trAEs with the highest pooled incidences were hypertension (11.1%, 95% CI: 4.0–29.0), neutropenia (10.5%, 95% CI: 7.0–15.4), and increased aspartate aminotransferase (7.7%, 95% CI: 6.3–9.4). The pooled incidence of trAEs leading to treatment discontinuation was 8.0% (95% CI: 6.0–10.5), and the overall incidence of treatment-related mortalities was 1.1%. &lt;b&gt;&lt;i&gt;Key Messages:&lt;/i&gt;&lt;/b&gt; This study comprehensively summarized the incidence and spectrum of trAEs in unresectable HCC patients receiving ICIs or ICI-based combinations in clinical trials. The results from this study will provide a useful reference to guide clinical practice.
Technical versus biological variability in a synthetic human gut community
Authors: Charlotte van de Velde, Clémence Joseph, Kenneth Simoens, Jeroen Raes, Kristel Bernaerts, Karoline Faust
Journal: Gut Microbes (2022)

Synthetic communities grown in well-controlled conditions are an important tool to decipher the mechanisms driving community dynamics. However, replicate time series of synthetic human gut communities in chemostats are rare, and it is thus still an open question to what extent stochasticity impacts gut community dynamics. Here, we address this question with a synthetic human gut bacterial community using an automated fermentation system that allows for a larger number of biological replicates. We collected six biological replicates for a community initially consisting of five common gut bacterial species that fill different metabolic niches. After an initial 12 hours in batch mode, we switched to chemostat mode and observed the community to stabilize after 2–3 days. Community profiling with 16S rRNA resulted in high variability across replicate vessels and high technical variability, while the variability across replicates was significantly lower for flow cytometric data. Both techniques agree on the decrease in the abundance of Bacteroides thetaiotaomicron, accompanied by an initial increase in Blautia hydrogenotrophica. These changes occurred together with reproducible metabolic shifts, namely a fast depletion of glucose and trehalose concentration in batch followed by a decrease in formic acid and pyruvic acid concentrations within the first 12 hours after the switch to chemostat mode. In conclusion, the observed variability in the synthetic bacterial human gut community, as assessed with 16S rRNA gene sequencing, is largely due to technical variability. The low variability seen in HPLC and flow cytometry data suggests a highly deterministic system.
Impact of SARS-CoV-2 exposure history on the T cell and IgG response
Authors: Roanne Keeton, Marius B. Tincho, Akiko Suzuki, Ntombi Benede, Amkele Ngomti, Richard Baguma, Masego V. Chauke, Mathilda Mennen, Sango Skelem, Marguerite Adriaanse, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Linda-Gail Bekker, Glenda Gray, Ntobeko A.B. Ntusi, Wendy A. Burgers, Catherine Riou
Journal: Cell Reports Medicine (2022)

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, from infection or vaccination, can potently boost spike antibody responses. Less is known about the impact of repeated exposures on T cell responses. Here, we compare the prevalence and frequency of peripheral SARS-CoV-2-specific T cell and immunoglobulin G (IgG) responses in 190 individuals with complex SARS-CoV-2 exposure histories. As expected, an increasing number of SARS-CoV-2 spike exposures significantly enhances the magnitude of IgG responses, while repeated exposures improve the number of T cell responders but have less impact on SARS-CoV-2 spike-specific T cell frequencies in the circulation. Moreover, we find that the number and nature of exposures (rather than the order of infection and vaccination) shape the spike immune response, with spike-specific CD4 T cells displaying a greater polyfunctional potential following hybrid immunity compared with vaccination only. Characterizing adaptive immunity from an evolving viral and immunological landscape may inform vaccine strategies to elicit optimal immunity as the pandemic progress.
Glucokinase activity in diabetes: too much of a good thing?
Authors: Frances M. Ashcroft, Matthew Lloyd, Elizabeth A. Haythorne
Journal: Trends in Endocrinology and Metabolism (2022)

Type 2 diabetes (T2D) is a global health problem characterised by chronic hyperglycaemia due to inadequate insulin secretion. Because glucose must be metabolised to stimulate insulin release it was initially argued that drugs that stimulate glucokinase (the first enzyme in glucose metabolism) would enhance insulin secretion in diabetes. However, in the long term, glucokinase activators have been largely disappointing. Recent studies show it is hyperactivation of glucose metabolism, not glucose itself, that underlies the progressive decline in beta-cell function in diabetes. This perspective discusses if glucokinase activators exacerbate this decline (by promoting glucose metabolism) and, counterintuitively, if glucokinase inhibitors might be a better therapeutic strategy for preserving beta-cell function in T2D.
The Fc-effector function of COVID-19 convalescent plasma contributes to SARS-CoV-2 treatment efficacy in mice
Authors: Irfan Ullah, Guillaume Beaudoin-Bussières, Kelly Symmes, Marc Cloutier, Eric Ducas, Alexandra Tauzin, Annemarie Laumaea, Michael W. Grunst, Katrina Dionne, Jonathan Richard, Philippe Bégin, Walther Mothes, Priti Kumar, Renée Bazin, Andrés Finzi, Pradeep D. Uchil
Journal: Cell Reports Medicine (2022)

COVID-19 convalescent plasmas (CCPs) are chosen for plasma therapy based on neutralizing titers and anti-Spike immunoglobulin levels. However, CCP characteristics that promote SARS-CoV-2 control are complex and incompletely defined. Using an in vivo imaging approach, we demonstrate that CCPs with low neutralizing (ID50 ≤ 1:250), but moderate to high Fc-effector activity, in contrast to those with poor Fc function, delay mortality and/or improve survival of SARS-CoV-2-challenged K18-hACE2 mice. The impact of innate immune cells on CCP efficacy depended on their residual neutralizing activity. Fractionation of a selected CCP revealed that IgG and Ig(M + A) were required during therapy, but the IgG fraction alone sufficed during prophylaxis. Finally, despite reduced neutralization, ancestral SARS-CoV-2-elicited CCPs significantly delayed Delta and Beta-induced mortality suggesting that Fc-effector functions contribute to immunity against VOCs. Thus, Fc activity of CCPs provide a second line of defense when neutralization is compromised and can serve as an important criterion for CCP selection.
Activins, follistatins and inhibins in postmenopausal osteoporosis: A proof of concept, case-control study
Authors: Athanasios D. Anastasilakis, Stergios A. Polyzos, Nikolaos E. Rodopaios, Polyzois Makras, Ajay Kumar, Bhanu Kalra, Christos S. Mantzoros
Journal: Metabolism (2022)
Generalized Pose Decoupled Network for Unsupervised 3D Skeleton Sequence-Based Action Representation Learning
Authors: Mengyuan Liu, Fanyang Meng, Yongsheng Liang
Journal: Cyborg and Bionic Systems (2022)

Human action representation is derived from the description of human shape and motion. The traditional unsupervised 3-dimensional (3D) human action representation learning method uses a recurrent neural network (RNN)-based autoencoder to reconstruct the input pose sequence and then takes the midlevel feature of the autoencoder as representation. Although RNN can implicitly learn a certain amount of motion information, the extracted representation mainly describes the human shape and is insufficient to describe motion information. Therefore, we first present a handcrafted motion feature called pose flow to guide the reconstruction of the autoencoder, whose midlevel feature is expected to describe motion information. The performance is limited as we observe that actions can be distinctive in either motion direction or motion norm. For example, we can distinguish "sitting down" and "standing up" from motion direction yet distinguish "running" and "jogging" from motion norm. In these cases, it is difficult to learn distinctive features from pose flow where direction and norm are mixed. To this end, we present an explicit pose decoupled flow network (PDF-E) to learn from direction and norm in a multi-task learning framework, where 1 encoder is used to generate representation and 2 decoders are used to generating direction and norm, respectively. Further, we use reconstructing the input pose sequence as an additional constraint and present a generalized PDF network (PDF-G) to learn both motion and shape information, which achieves state-of-the-art performances on large-scale and challenging 3D action recognition datasets including the NTU RGB+D 60 dataset and NTU RGB+D 120 dataset.
The transcription factor ATF4 mediates endoplasmic reticulum stress-related podocyte injury and slit diaphragm defects
Authors: Vanessa Krausel, Lisanne Pund, Harald Nüsse, Hussein Bachir, Andrea Ricker, Jürgen Klingauf, Thomas Weide, Hermann Pavenstädt, Michael P. Krahn, Daniela A. Braun
Journal: Kidney International (2022)
The Jasmine (<i>Jasminum Sambac</i>) Genome Provides Insight into the Biosynthesis of Flower Fragrances and Jasmonates
Authors: Gang Chen, Salma Mostafa, Zhaogeng Lu, Ran Du, Jiawen Cui, Yun Wang, Qinggang Liao, Jinkai Lu, Xinyu Mao, Bang Chang, Quan Gan, Li Wang, Zhichao Jia, Xiulian Yang, Yingfang Zhu, Jianbin Yan, Biao Jin
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract Jasminum sambac (jasmine flower), a world-renowned plant appreciated for its exceptional flower fragrance, is of cultural and economic importance. However, the genetic basis of its fragrance is largely unknown. Here, we present the first de novo genome assembly of J. sambac with 550.12 Mb (scaffold N50 = 40.10 Mb) assembled into 13 pseudochromosomes. Terpene synthase (TPS) genes associated with flower fragrance are considerably amplified in the form of gene clusters through tandem duplications in the genome. Gene clusters within the salicylic acid/benzoic acid/theobromine (SABATH) and benzylalcohol O-acetyltransferase/anthocyanin O-hydroxycinnamoyltransferases/anthranilate N-hydroxycinnamoyl/benzoyltransferase/deacetylvindoline 4-O-acetyltransferase (BAHD) superfamilies were identified to be related to the biosynthesis of phenylpropanoid/benzenoid compounds. Several key genes involved in jasmonate biosynthesis were duplicated, causing an increase in copy numbers. In addition, multi-omics analyses identified various aromatic compounds and many genes involved in fragrance biosynthesis pathways. Furthermore, the roles of JsTPS3 in β-ocimene biosynthesis, as well as JsAOC1 and JsAOS in jasmonic acid biosynthesis, were functionally validated. The genome assembled in this study for J. sambac offers a basic genetic resource for studying floral scent and jasmonate biosynthesis, and provides a foundation for functional genomic research and variety improvements in Jasminum.
Impact of vaccination on the presence and severity of symptoms in hospitalized patients with an infection of the Omicron variant (B.1.1.529) of the SARS-CoV-2 (subvariant BA.1)
Authors: Guillaume Beraud, Laura Bouetard, Rok Civljak, Jocelyn Michon, Necla Tulek, Sophie Lejeune, Romain Millot, Aurélie Garchet-Beaudron, Maeva Lefebvre, Petar Velikov, Benjamin Festou, Sophie Abgrall, Ivan K. Lizatovic, Aurélie Baldolli, Huseyin Esmer, Sophie Blanchi, Gabrielle Froidevaux, Nikol Kapincheva, Jean-François Faucher, Mario Duvnjak, Elçin Afşar, Luka Švitek, Saliha Yarimoglu, Rafet Yarimoglu, Cécile Janssen, Olivier Epaulard
Journal: Clinical Microbiology and Infection (2022)
The efficacy and safety of systemic corticosteroids as first line treatment for granulomatous lymphocytic interstitial lung disease
Authors: Bas Smits, Sigune Goldacker, Suranjith Seneviratne, Marion Malphettes, Hilary Longhurst, Omar E. Mohamed, Carla Witt-Rautenberg, Lucy Leeman, Eva Schwaneck, Isabelle Raymond, Kilifa Meghit, Annette Uhlmann, Christine Winterhalter, Joris van Montfrans, Marion Klima, Sarita Workman, Claire Fieschi, Lorena Lorenzo, Sonja Boyle, Shamin Onyango-Odera, Suzanne Price, Marc Schmalzing, Valerie Aurillac, Antje Prasse, Ieneke Hartmann, Jennifer J. Meerburg, Mariette Kemner-van de Corput, Harm Tiddens, Bodo Grimbacher, Peter Kelleher, Smita Y. Patel, Anne-Sophie Korganow, Jean-Francois Viallard, Hans-Peter Tony, Claire Bethune, Hendrik Schulze-Koops, Torsten Witte, Aarnoud Huissoon, Helen Baxendale, Sofia Grigoriadou, Eric Oksenhendler, Siobhan O. Burns, Klaus Warnatz
Journal: Journal of Allergy and Clinical Immunology (2022)
The gut microbiome is a significant risk factor for future chronic lung disease
Authors: Yang Liu, Shu Mei Teo, Guillaume Méric, Howard H.F. Tang, Qiyun Zhu, Jon G. Sanders, Yoshiki Vázquez-Baeza, Karin Verspoor, Ville A. Vartiainen, Pekka Jousilahti, Leo Lahti, Teemu Niiranen, Aki S. Havulinna, Rob Knight, Veikko Salomaa, Michael Inouye
Journal: Journal of Allergy and Clinical Immunology (2022)

The gut-lung axis is generally recognized, but there are few large studies of the gut microbiome and incident respiratory disease in adults.We sought to investigate the association and predictive capacity of the gut microbiome for incident asthma and chronic obstructive pulmonary disease (COPD).Shallow metagenomic sequencing was performed for stool samples from a prospective, population-based cohort (FINRISK02; N = 7115 adults) with linked national administrative health register-derived classifications for incident asthma and COPD up to 15 years after baseline. Generalized linear models and Cox regressions were used to assess associations of microbial taxa and diversity with disease occurrence. Predictive models were constructed using machine learning with extreme gradient boosting. Models considered taxa abundances individually and in combination with other risk factors, including sex, age, body mass index, and smoking status.A total of 695 and 392 statistically significant associations were found between baseline taxonomic groups and incident asthma and COPD, respectively. Gradient boosting decision trees of baseline gut microbiome abundance predicted incident asthma and COPD in the validation data sets with mean area under the curves of 0.608 and 0.780, respectively. Cox analysis showed that the baseline gut microbiome achieved higher predictive performance than individual conventional risk factors, with C-indices of 0.623 for asthma and 0.817 for COPD. The integration of the gut microbiome and conventional risk factors further improved prediction capacities.The gut microbiome is a significant risk factor for incident asthma and incident COPD and is largely independent of conventional risk factors.
Performance of discs, sensititre EUMDROXF microplates and MTS gradient strips for the determination of the susceptibility of multidrug-resistant Pseudomonas aeruginosa to cefiderocol
Authors: Léa Devoos, Adrien Biguenet, Julie Rousselot, Maxime Bour, Patrick Plésiat, Damien Fournier, Katy Jeannot
Journal: Clinical Microbiology and Infection (2022)
Oncolytic virus-based hepatocellular carcinoma treatment: Current status, intravenous delivery strategies, and emerging combination therapeutic solutions
Authors: Xinguo Li, Xiaonan Sun, Bingyuan Wang, Yiling Li, Jing Tong
Journal: Asian Journal of Pharmaceutical Sciences (2022)

Current treatments for advanced hepatocellular carcinoma (HCC) have limited success in improving patients' quality of life and prolonging life expectancy. The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies. Recently, there has been increased interest in oncolytic viruses (OVs) as a therapeutic modality for HCC. OVs undergo selective replication in cancerous tissues and kill tumor cells. Strikingly, pexastimogene devacirepvec (Pexa-Vec) was granted an orphan drug status in HCC by the U.S. Food and Drug Administration (FDA) in 2013. Meanwhile, dozens of OVs are being tested in HCC-directed clinical and preclinical trials. In this review, the pathogenesis and current therapies of HCC are outlined. Next, we summarize multiple OVs as single therapeutic agents for the treatment of HCC, which have demonstrated certain efficacy and low toxicity. Emerging carrier cell-, bioengineered cell mimetic- or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described. In addition, we highlight the combination treatments between oncolytic virotherapy and other modalities. Finally, the clinical challenges and prospects of OV-based biotherapy are discussed, with the aim of continuing to develop a fascinating approach in HCC patients.